Endothelial cells control pancreatic cell fate at defined stages through EGFl7 signaling

Der I. Kao, Lauretta A. Lacko, Bi Sen Ding, Chen Huang, Kathleen Phung, Guoqiang Gu, Shahin Rafii, Heidi Stuhlmann, Shuibing Chen

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Although endothelial cells have been shown to affect mouse pancreatic development, their precise function in human development remains unclear. Using a coculture system containing human embryonic stem cell (hESC)-derived progenitors and endothelial cells, we found that endothelial cells play a stage-dependent role in pancreatic development, in which they maintain pancreatic progenitor (PP) self-renewal and impair further differentiation into hormone-expressing cells. The mechanistic studies suggest that the endothelial cells act through the secretion of EGFL7. Consistently, endothelial overexpression of EGFL7 in vivo using a transgenic mouse model resulted in an increase of PP proliferation rate and a decrease of differentiation toward endocrine cells. These studies not only identified the role of EGFL7 as the molecular handle involved in the crosstalk between endothelium and pancreatic epithelium, but also provide a paradigm for using hESC stepwise differentiation to dissect the stage-dependent roles of signals controlling organogenesis.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalStem Cell Reports
Volume4
Issue number2
DOIs
StatePublished - 10 Feb 2015
Externally publishedYes

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